Scientific Merit; The goal of the proposed studies is to elucidate the signalling mechanisms involved in the activation of the transcription factor NF-kB. NF-kB is an inducible factor that is held in an inactive state i the cytoplasm by the inhibitory protein IkB. Exposure of cells to appropriate stimuli results in rapid phosphorylation and subsequent degradation of IkB with a resulting translocation of NF-kB to the nucleus, where it is involved in activation of gene transcription. The candidate proposes to identify the protein kinase that is responsible for phosphorylating IkB and then to study the mechanism of activation of this kinase. As a longer term goal, he will attempt to trace the signal transduction pathways for NF-kB back to cell surface receptors.